Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data from various laboratories have indicated associations of various alleles determined by RFLPs within or adjacent to several apolipoprotein genes with abnormalities in plasma lipids and/or premature coronary artery disease (CAD). In order to assess such relationships we have examined allele frequencies of 8 different RFLPs within or adjacent to the apo A-I, C-III and A-IV gene complex on the long arm of chromosome 11 (MspI, 5' to the apo A-I gene; MspI, within the apo A-I gene; PstI, 3' to the apo A-I gene; SstI, 3' to the apo C-III gene; PvuII, within the apo C-III gene; PvuII, 5' to the apo C-III gene; XbaI, within the apo A-IV gene; and XbaI, 3' to the apo A-IV gene) in 202 patients with CAD (50% narrowing of one or more coronary arteries) prior to age 60 and 145 normal controls. None of the allele frequencies of these RFLPs were significantly different in cases as compared to controls. With regard to associations with plasma lipids and apolipoprotein levels, the rare allele determined by the absence of the PstI site was associated with elevated triglyceride levels (P less than 0.05) in cases, but not in controls. In contrast, the rate MspI allele 5' to the apo A-I gene was associated with elevated triglyceride levels (P less than 0.05) in controls but not in cases. In both cases and controls, subjects with the uncommon SstI allele had triglyceride levels that were 9 and 38% higher than in those without this allele. These differences were significant (P less than 0.05) only in controls. Our data indicate that the rare allele determined by the SstI site within this gene complex deserves further study in order to understand its association with elevated triglycerides in Caucasian populations. However, at the present time all these DNA markers lack sufficient specificity to be clinically useful for CAD risk assessment.
Atherosclerosis 1991 Mar
PMID:Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature coronary artery disease. 167 4

A high frequency restriction fragment length polymorphism (RFLP) at the 3'-end of the pigeon pro alpha 2(1) collagen gene was detected using the restriction endonuclease EcoR1. The distribution of this allelic variant was analyzed in DNA isolated from White Carneau pigeons genetically susceptible to the development of spontaneous atherosclerosis. The atherogenic phenotype in individual pigeons was measured by the determination of total cholesterol and cholesterol ester levels in the celiac focus of the thoracic aorta of adult White Carneau pigeons. Aortic wall cholesterol levels correlated with an increase in lesion size. No correlation, however, was observed between allelic variants of the pigeon pro alpha 2(1) collagen gene and the atherogenic phenotype in White Carneau pigeons suggesting lack of linkage between this allelic marker and the genetic susceptibility to spontaneous atherogenesis. This is the first study of its kind in this animal model and serves to provide a basis for the further analysis of co-segregation of RFLPS in candidate genes to this polygenic phenotype.
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PMID:A restriction fragment length polymorphism in the pigeon pro alpha 2(1) collagen gene: lack of an allelic association with an atherogenic phenotype in pigeons genetically susceptible to the development of spontaneous atherosclerosis. 168 10

Three DNA polymorphisms (XbaI, EcoRI, MspI) in the 3'-end of the apolipoprotein B gene were studied in relation to atherosclerosis, lipoprotein levels and age in three groups of atherosclerotic individuals and in nonatherosclerotic controls. The atherosclerotic groups comprised a postmyocardial infarction group with a mean age of 48 years, a group of individuals operated on for carotid stenosis with a mean age of 62 years, and a group of 85-year-olds with clinical coronary artery disease, peripheral arterial disease, or both. All 311 individuals were unrelated Caucasians of Danish ancestry. For the XbaI polymorphism, the X- allele was an independent predictor for myocardial infarction on multivariate analysis, but did not distinguish between patients and controls on univariate analysis. Additionally, this polymorphism was associated with variation in lipoprotein levels, but there was no clear evidence of a gene dosage effect. For the EcoRI polymorphism, the E- allele was associated with elevated levels of VLDL cholesterol, plasma triglycerides and VLDL triglycerides. Similar, but weaker associations were found for the MspI polymorphism. There were no significant differences in allele frequencies as a function of age for any of the DNA polymorphisms. In conclusion, while variation associated with the EcoRI polymorphism appears to be involved in the regulation of VLDL metabolism, variation associated with the XbaI polymorphism may determine susceptibility to coronary artery disease independent of other conventional risk factors, but it also appears to affect variation in lipoprotein levels.
Atherosclerosis 1991 Jul
PMID:Variation of apolipoprotein B gene is associated with myocardial infarction and lipoprotein levels in Danes. 168 18

We present here rapid and efficient methods for the analysis of multiple variable apolipoprotein (apo) B loci using polymerase chain reaction based techniques. For illustrative purposes, we have applied these methods to establish an association between these polymorphisms and the apo B Ag immunological epitopes. The 5 DNA polymorphisms include 3 restriction endonuclease sites (for XbaI, EcoRI and MspI), a variable number of tandem repeat (VNTR) locus at the 3' end of the apo B gene, and an insertion/deletion polymorphism involving the signal peptide region of apo B. The latter two newly described polymorphisms are directly detectable following amplification and may have physiological effects on apo B expression because of their critical locations. All of these sites were typed using flanking oligonucleotides and the newly developed polymerase chain reaction. Amplification products were typed either directly (3' VNTR and signal peptide insertion/deletion alleles), or following specific enzyme digestion (for the restriction sites), or by allele specific oligonucleotides. The detailed methods presented will prove generally useful for rapidly typing DNA variation in the apo B gene. Using these techniques, we found a significant linkage disequilibrium between the Ag(t/z) locus and the 3' VNTR, and the Ag(c/g) locus and the signal peptide length polymorphism. Future association studies using these DNA polymorphisms should take into consideration that observed effects may be related to its linkage disequilibrium with the Ag loci and vice versa.
Atherosclerosis 1990 Apr
PMID:Rapid typing of apolipoprotein B DNA polymorphisms by DNA amplification. Association between Ag epitopes of human apolipoprotein B-100, a signal peptide insertion/deletion polymorphism, and a 3'flanking DNA variable number of tandem repeats polymorphism of the apolipoprotein B gene. 169 6

Vascular cell adhesion molecule 1 (VCAM-1) is a cell surface glycoprotein adhesive for certain blood leukocytes and tumor cells, which is expressed by activated endothelium in a variety of pathologic conditions including atherosclerosis. Genomic clones encoding the VCAM1 gene were isolated and the organization of the gene was determined. The gene, which is present in a single copy in the human genome, contains 9 exons spanning approximately 25 kilobases of DNA. Exons 2-8 contain C2 or H-type immunoglobulin domains. At least two different VCAM-1 precursors can be generated from the human gene as a result of alternative mRNA splicing events, which include or exclude exon 5. A consensus TATAA element is located upstream of the transcriptional start site. The VCAM1 promoter contains consensus binding sites for NF-kappa B, the GATA family of transcription factors, as well as an AP1 site. The VCAM1 gene was assigned to the 1p31-32 region of chromosome 1 based on the analysis of human-mouse hybrid cell lines and in situ hybridization. Structural analysis of the human VCAM1 gene provides the basis for alternative mRNA splicing and an initial approach to elucidating the regulation of VCAM-1 expression.
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PMID:Gene structure, chromosomal location, and basis for alternative mRNA splicing of the human VCAM1 gene. 171 83

The effects of prostacyclin and its stable analogues on endothelin-induced DNA synthesis were investigated in cultured vascular smooth muscle cells. Aortic smooth muscle cells were obtained from male Wistar rats. In order to eliminate endothelial cells, the cells were cloned. DNA synthesis in intact cells was estimated by [3H]thymidine incorporation. Prostacyclin and its stable analogues (TEI-7165, TEI-9090, TEI-1324, TEI-3356, and TEI-9063) inhibited the endothelin-induced DNA synthesis with an IC50 of 1-30 nM. These results indicate that prostacyclin and its stable analogues are possibly effective in preventing the proliferation of vascular smooth muscle cells under some pathological situations, including atherosclerosis.
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PMID:Inhibition of endothelin-1-induced DNA synthesis by prostacyclin and its stable analogues in vascular smooth muscle cells. 172 24

This article describes investigations of several aspects of the molecular biology of the human renin gene and the three-dimensional structure of renin and its precursor, prorenin. Because of the importance of the RAS in hypertension, heart failure, renal failure, and possibly other disorders such as atherosclerosis, it is critical to understand the detailed control of this system. This control involves regulation at the transcriptional level, folding of prorenin, sorting of prorenin to a regulated pathway where it is proteolytically cleaved to renin and released in response to secretogogues, constitutive release of uncleaved prorenin, and nonproteolytic activation of prorenin. Currently there is great interest not only in the control of renin in the kidney, the sole source of circulating renin, but also at extrarenal sites where RAS activity may regulate cardiovascular functions. The renin gene was found to be expressed significantly in the renal juxtaglomerular cells and several other cell types. Most tissue culture cells did not express the gene; exceptions were cultured SK-LMS-1 cells and cAMP-stimulated human lung fibroblasts. Cultured human uterine-placental cells expressed the human renin gene at levels higher than in other cell types assessed. Renin mRNA had the same start site in the placental cells as the kidney and was regulated by calcium ionophores and cAMP. Thus, these cells provide primary nontransformed human cells to study the homologous human promoter. Transfected renin promoters showed cell type-specific expression and cAMP responsiveness in these cells in constructs containing as few as 102 bp of 5'-flanking DNA. DNA upstream from this appears to contain an inhibitory element(s) that may have some tissue specificity in its distribution. The cAMP response is not due to cAMP induction of a transcription factor that secondarily affects the renin promoter. A novel element may be involved, since the promoter does not contain a CRE element that mediates many cAMP responses, and the cells do not appear to respond to another known cAMP-responsive transcription factor, AP-2. Studies with transfected vectors expressing a mutant cAMP-responsive protein kinase A regulatory subunit suggest that cAMP is not responsible for basal renin promoter activity in the placental cells. By contrast, cAMP induces in essence gene activation in WI26VA4 transformed human lung fibroblasts in which renin mRNA levels increase by up to 150-fold in response to forskolin. Thus, cAMP may activate renin gene expression under certain circumstances and tissue-specific renin gene expression may be directed by more than one mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Molecular biology of human renin and its gene. 174 21

The Watanabe Heritable Hyperlipidemic (WHHL) rabbit is a widely studied animal model for the human genetic disorder familial hypercholesterolemia, and spontaneously develops atherosclerotic disease. We studied the growth characteristics of cultured vascular smooth muscle cells (VSMC) from WHHL rabbits compared with VSMC from Japanese white rabbits. We measured cell proliferation, DNA synthesis, and c-myc proto-oncogene expression, in response to growth stimuli such as fetal bovine serum (FBS) and platelet-derived growth factor (PDGF). VSMC from Japanese white rabbits exhibited a 4-fold increase in cell numbers during a 5-day incubation period compared with those from WHHL rabbits. FBS and PDGF stimulated DNA synthesis, as measured by thymidine incorporation into VSMC, in both Japanese white rabbits and WHHL rabbits, however the response was significantly higher in the former strain. The intracellular pH value of VSMC determined using the pH-sensitive fluorescence dye 2',7'-bis-carboxyethyl-carboxyfluorescein was significantly higher in WHHL rabbits than in Japanese white rabbits. Proto-oncogene c-myc was induced by exposure of VSMC to FBS, however there was no significant difference in c-myc mRNA levels between the two strains. These results suggest that VSMC from WHHL rabbits are not genetically growth accelerated, but show decreased growth response to growth stimuli.
Atherosclerosis 1991 Oct
PMID:Vascular smooth muscle cells from genetically hyperlipidemic rabbit (WHHL rabbit) exhibit decreased growth response. 175 82

Oxidative stress is strongly implicated in a number of diseases, such as rheumatoid arthritis, inflammatory bowel disorders, and atherosclerosis, and its emerging as one of the most important causative agents of mutagenesis, tumorigenesis, and aging. Recent progress on the genetics and molecular biology of the cellular responses to oxidative stress, primarily in Escherichia coli and Salmonella typhimurium, is summarized. Bacteria respond to oxidative stress by invoking two distinct stress responses, the peroxide stimulon and the superoxide stimulon, depending on whether the stress is mediated by peroxides or the superoxide anion. The two stimulons each contain a set of more than 30 genes. The expression of a subset of genes in each stimulon is under the control of a positive regulatory element; these genes constitute the OxyR and SoxRS regulons. The schemes of regulation of the two regulons by their respective regulators are reviewed in detail, and the overlaps of these regulons with other stress responses such as the heat shock and SOS responses are discussed. The products of Oxy-R- and SoxRS-regulated genes, such as catalases and superoxide dismutases, are involved in the prevention of oxidative damage, whereas others, such as endonuclease IV, play a role in the repair of oxidative damage. The potential roles of these and other gene products in the defense against oxidative damage in DNA, proteins, and membranes are discussed in detail. A brief discussion of the similarities and differences between oxidative stress responses in bacteria and eukaryotic organisms concludes this review.
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PMID:Oxidative stress responses in Escherichia coli and Salmonella typhimurium. 177 27

We describe a rapid screening procedure to identify known DNA sequence changes in individuals diagnosed as having heterozygous familial hypercholesterolaemia (FH). The screening is made possible by combining a rapid DNA extraction protocol and small scale polymerase chain reaction DNA amplification, followed by oligonucleotide melting or restriction enzyme digestion. We have screened for two different mutations; firstly a mutation in the apolipoprotein B (apo B) gene that results in the substitution of glutamine (Gln) for arginine (Arg) at amino acid residue 3500 (apo B3500 mutation). Apo B is the principal component of the protein moiety of low density lipoprotein (LDL) and the mutation reduces the affinity for the LDL receptor (LDL-R). Secondly we have screened for a point mutation in the LDL-R gene itself that creates a new Pst I restriction enzyme site. This mutation in the LDL-R gene (LDL-R664 mutation) results in the substitution of leucine (Leu) for proline (Pro) at amino acid 664 and is known to slow processing of the LDL-R precursor to the mature form and to reduce the affinity of the receptor on the cell surface for LDL. In 77 unrelated patients with a clinical diagnosis of FH two out of 77 (2.6%) were positive for the apo B3500 mutation. Three (3.9%) were positive for the LDL-R664 mutation. Thus these two mutations might account for 5-6% of patients in the U.K. with a clinical diagnosis of FH (5000-6000 people).(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1991 Aug
PMID:Rapid screening for specific mutations in patients with a clinical diagnosis of familial hypercholesterolaemia. 179 40


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